Mechanism of Action
(cont’d)
5.CELL WALL SYNTHESIS INHIBITORS β-Lactam Antibiotics
Penicillins
Cephalosporins
Carbapenems
Monobactams
Mechanism of Action
CELL WALL SYNTHESIS INHIBITORS
(cont’d)
β-Lactam ring structure
Mechanism of Action
CELL WALL SYNTHESIS INHIBITORS
(cont’d)
Action of β-Lactam antibiotics
1.Bactericidal; growing cells only
2.Drug links covalently to regulatory enzymes called PBPs (penicillin- binding proteins)
3.Blocks cross-linkage of peptidoglycan
Mechanism of Action
CELL WALL SYNTHESIS INHIBITORS
(cont’d)
Action of β-Lactam antibiotics For E. coli
>MIC
wall damage
autolysins
spheroplasting
cell lysis
< MIC
no septa
filaments
Mechanism of Action
CELL WALL SYNTHESIS INHIBITORS
(cont’d)
Resistance to β-Lactams – Gram pos.
Mechanism of Action
CELL WALL SYNTHESIS INHIBITORS
(cont’d)
Resistance to β-Lactams – Gram neg.
Mechanism of Action |
|
|
CELL WALL SYNTHESIS INHIBITORS |
(cont’d) |
|
Non - β-Lactams |
||
|
Vancomycin
active against gram positive cocci, but not gram negative because too large to pass through outer membrane
interferes with PG elongation
Cycloserine, ethionamide and isoniazid
inhibits enzymes that catalyze cell wall synthesis
for Mycobacterial infections
Clinical Uses
PATHOGENS |
TYPICAL DRUG |
|
|
Gram positive |
|
Pen-ase (-) |
Penicillin G (oral or IM) |
Pen-ase (+) |
Methicillin, Nafcillin |
Gram negative |
|
Enterics, etc. |
Ampicillin, gentamicin, etc. |
Pseudomonas |
Ticarcillin, tobramycin |
B. fragilis |
Clindamycin |